Ampullary Carcinoma

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Practice Essentials

Carcinoma of the ampulla of Vater is a malignant tumor arising in the last centimeter of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. Treatment fails in nearly 70% of patients with poor prognostic features.

Signs and symptoms

The signs and symptoms of ampullary carcinoma include the following:

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies

Routine laboratory studies include the following:

Ultrasonography of the abdomen

CT scanning of the abdomen and/or pelvis

Other imaging studies

See Workup for more detail.

Management

The standard surgical approach to the treatment of ampullary carcinoma is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the gastric antrum and duodenum; a segment of the first portion of the jejunum, gallbladder, and distal common bile duct; the head and often the neck of the pancreas; and adjacent regional lymph nodes.

The operative mortality rate for pancreaticoduodenectomy was at one time reported to be approximately 20%, but several hospital centers have since reported large series with operative mortality rates in the range of 5%.

See Treatment for more detail.

Background

Carcinoma of the ampulla of Vater is a malignant tumor arising in the last centimeter of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. The pancreatic duct (of Wirsung) and common bile duct merge and exit by way of the ampulla into the duodenum. The ductal epithelium in these areas is columnar and resembles that of the lower common bile duct.

Adenocarcinoma of the ampulla of Vater is relatively uncommon, accounting for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas.

Pathophysiology

The periampullary region is anatomically complex, representing the junction of 3 different epithelia, pancreatic ducts, bile ducts, and duodenal mucosa. Grossly, carcinomas originating in the ampulla of Vater can arise from 1 of 4 epithelial types: (1) terminal common bile duct, (2) duodenal mucosa, (3) pancreatic duct, or (4) ampulla of Vater.

Distinguishing between true ampullary cancers and periampullary tumors is critical to understanding the biology of these lesions. Each type of mucosa produces a different pattern of mucus secretion. In a complete histochemical study, Dawson and Connolly divided acid mucins into sulphomucins and sialomucins; in general, ampullary cancers produce sialomucins, whereas periampullary tumors secrete sulfated mucins. These researchers demonstrated that ampullary tumors secreting sialomucins had a better prognosis (100% vs 27% 5-y survival rate).[1] Other investigators have confirmed the prognostic power of the pattern of mucin secretion.

Carter et al suggest that, histologically, ampullary tumors can be classified as either pancreaticobiliary or intestinal, and that the clinical behavior of these tumors reflects this classification; the course of intestinal ampullary adenocarcinomas is similar to that of their duodenal counterparts, whereas pancreaticobiliary tumors follow a more aggressive course, similar to that of pancreatic adenocarcinomas.[2]

Immunohistochemical stains for expressions of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, Ki-67, and p53 have been studied for prognostic power. In a series of 45 patients, expression of CA 19-9 labeling intensity and apical localization both were statistically significant predictors of poor prognosis. The 5-year survival rates were markedly different between tumors that expressed CA 19-9 and those that did not (36% vs 100%).[3] CEA expression also might be a marker for prognosis, but it is much weaker. Ki-67 and p53 were not demonstrated to have an effect on outcome. Research along these avenues ultimately might provide the rationale for discriminative administration of adjuvant therapy.

Epidemiology

Frequency

United States

Adenocarcinoma of the ampulla of Vater is a relatively uncommon tumor that accounts for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas. A review of data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program found 5,625 cases of ampullary cancer between 1973 and 2005; the frequency of the disease has been increasing since 1973.[4]

Mortality/Morbidity

Pancreaticoduodenectomy is a formidable operation, and the morbidity and mortality rates associated with this procedure historically have been high.

Race

Because carcinoma of the ampulla of Vater is relatively uncommon, studies of the patterns of occurrence among different ethnic groups have not been conducted.

Sex

Ampullary cancer is more common in men, according to the National Cancer Institute’s SEER Program.[4]

History

Physical

Laboratory Studies

Imaging Studies

Staging

Over the years, multiple systems for staging this tumor have been proposed.

Table 1. Staging of Ampullary Cancers by the TNM System


View Table

See Table

Surgical Care

The standard surgical approach is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the gastric antrum and duodenum; a segment of the first portion of the jejunum, gallbladder, and distal common bile duct; the head and often the neck of the pancreas; and adjacent regional lymph nodes.

In a review of 450 cases of surgical resection of ampullary adenoma or adenocarcinoma at Johns Hopkins, Winter et al found that 96.7% of the patients had undergone pancreaticoduodenectomy rather than local excision. These researchers concluded that pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection, given that nearly 30% of the Johns Hopkins patients with T1 disease had lymph node metastases. Factors associated with the presence of lymph node metastasis included tumor size ≥ 1 cm (odds ratio [OR] 2.1), poor histologic grade (OR 4.8), perineural invasion (OR 3.0), microscopic vessel invasion (OR 6.6), and depth of invasion > pT1 (OR 4.3; all P < 0.05). Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P < 0.001).[7, 8]

Results after radical resection of ampullary of Vater carcinoma have been improving. During the past decade, 5-year survival rates have ranged from 20-61%, averaging higher than 35%. The reported mortality rates from this operation are decreasing. A summary follows in Table 2.

Table 2. Results of Pancreaticoduodenal Resection for Carcinoma of the Ampulla of Vater


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See Table

Table 3. Summary of 5-Year Survival After Resection for Lymph Node Negative and Positive Carcinoma of the Ampulla of Vater


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Further Outpatient Care

Author

Vivek K Mehta, MD, Radiation Oncologist, Director, Center for Advanced Targeted Radiotherapies, Department of Radiation Oncology, Swedish Cancer Institute, Seattle, Washington

Disclosure: Nothing to disclose.

Specialty Editors

Clarence Sarkodee-Adoo, MD, Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Disclosure: Nothing to disclose.

Additional Contributors

Coauthor(s): George Fisher, MD, PhD, Associate Professor, Department of Internal Medicine, Division of Medical Oncology, Stanford University School of Medicine

References

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StageTNM
Stage 0TisN0M0
Stage IT1N0M0
Stage IIT2-3N0M0
Stage IIIT1-3N1M0
Stage IVT4N0-1M0
T1-4N0-1M1
InstitutionYearPatients, #Resected, #Mortality Rate, %5-Year Survival Rate, %
Cleveland Clinic[9] 1950-19845959837
Leicester Royal Infirmary, United Kingdom[10] 1972-198452241356
University of Alabama[11] 1953-198824241361
Mayo Clinic[12] 1965-19891041045.734
Montebelluna Hospital, Italy[13] 1971-19903631356
Veterans Affairs hospitals[14] 1971-1993123641420
Academic Medical Center, Amsterdam[15] 1984-19926762650
Hanover Hospital, Germany[16] 1971-19938785938
Johns Hopkins[17] 1969-1996120106438
Memorial Sloan-Kettering[18] 1983-1995123101544
Catholic University, Italy[19] 1981-20029464964
InstitutionNode-Negative, % (#)Node-Positive, % (#)P Value
University of Alabama at Birmingham[11] 78 (19)50 (5)Not significant
Mayo Clinic, Minnesota[12] 43 (53)16 (50).001
Montebelluna Hospital, Italy[13] 64 (22)0 (9).36
Academic Medical Center, Amsterdam[15] 59 (32)41 (35).05
Niigata University, Japan[20] 81 (17)41 (18)< .01
Johns Hopkins, Baltimore[17] 43 (53)31 (50).05
Kanazawa University Hospital, Japan[21] 74 (21)31 (15)< .05
Memorial Sloan- Kettering, New York[18] 55 (55)30 (46).04
Loyola University, Chicago[28] 78 (27)25 (24)< 0.05